Axon-like protrusions promote small cell lung cancer migration and metastasis
Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that t...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2019-12-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/50616 |
| _version_ | 1811181005941243904 |
|---|---|
| author | Dian Yang Fangfei Qu Hongchen Cai Chen-Hua Chuang Jing Shan Lim Nadine Jahchan Barbara M Grüner Christin S Kuo Christina Kong Madeleine J Oudin Monte M Winslow Julien Sage |
| author_facet | Dian Yang Fangfei Qu Hongchen Cai Chen-Hua Chuang Jing Shan Lim Nadine Jahchan Barbara M Grüner Christin S Kuo Christina Kong Madeleine J Oudin Monte M Winslow Julien Sage |
| author_sort | Dian Yang |
| collection | DOAJ |
| description | Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC. |
| first_indexed | 2024-04-11T09:12:17Z |
| format | Article |
| id | doaj.art-fda050c064b3492b90714973d6d4255b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:12:17Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fda050c064b3492b90714973d6d4255b2022-12-22T04:32:29ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.50616Axon-like protrusions promote small cell lung cancer migration and metastasisDian Yang0Fangfei Qu1Hongchen Cai2Chen-Hua Chuang3Jing Shan Lim4Nadine Jahchan5Barbara M Grüner6https://orcid.org/0000-0003-0974-4826Christin S Kuo7Christina Kong8Madeleine J Oudin9Monte M Winslow10Julien Sage11https://orcid.org/0000-0002-8928-9968Cancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United StatesDepartment of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United StatesDepartment of Genetics, Stanford University School of Medicine, Stanford, United StatesDepartment of Genetics, Stanford University School of Medicine, Stanford, United StatesCancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United StatesDepartment of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United StatesDepartment of Genetics, Stanford University School of Medicine, Stanford, United States; Department of Pathology, Stanford University School of Medicine, Stanford, United States; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK) partner site Essen, Essen, GermanyDepartment of Pediatrics, Stanford University School of Medicine, Stanford, United StatesDepartment of Pathology, Stanford University School of Medicine, Stanford, United StatesDepartment of Biomedical Engineering, Tufts University, Medford, United StatesCancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United States; Department of Pathology, Stanford University School of Medicine, Stanford, United StatesCancer Biology Program, Stanford University School of Medicine, Stanford, United States; Department of Pediatrics, Stanford University School of Medicine, Stanford, United States; Department of Genetics, Stanford University School of Medicine, Stanford, United StatesMetastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.https://elifesciences.org/articles/50616SCLCneuroendocrineneuronalprotrusionsmigrationmetastasis |
| spellingShingle | Dian Yang Fangfei Qu Hongchen Cai Chen-Hua Chuang Jing Shan Lim Nadine Jahchan Barbara M Grüner Christin S Kuo Christina Kong Madeleine J Oudin Monte M Winslow Julien Sage Axon-like protrusions promote small cell lung cancer migration and metastasis eLife SCLC neuroendocrine neuronal protrusions migration metastasis |
| title | Axon-like protrusions promote small cell lung cancer migration and metastasis |
| title_full | Axon-like protrusions promote small cell lung cancer migration and metastasis |
| title_fullStr | Axon-like protrusions promote small cell lung cancer migration and metastasis |
| title_full_unstemmed | Axon-like protrusions promote small cell lung cancer migration and metastasis |
| title_short | Axon-like protrusions promote small cell lung cancer migration and metastasis |
| title_sort | axon like protrusions promote small cell lung cancer migration and metastasis |
| topic | SCLC neuroendocrine neuronal protrusions migration metastasis |
| url | https://elifesciences.org/articles/50616 |
| work_keys_str_mv | AT dianyang axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT fangfeiqu axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT hongchencai axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT chenhuachuang axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT jingshanlim axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT nadinejahchan axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT barbaramgruner axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT christinskuo axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT christinakong axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT madeleinejoudin axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT montemwinslow axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis AT juliensage axonlikeprotrusionspromotesmallcelllungcancermigrationandmetastasis |